Pathologic changes in the arterial intima occur in animals subjected to various forms of hypertension and neuropsychologic stress, and the pathologic features exhibit great similarity in the reaction to both of these physiologic states. The proposed research, utilizing primarily quantitative ultrastructural and biochemical techniques applied to rat blood vessels, will seek (1) to identify specific physiologic antecedents to the intimal reaction and (2) to characterize the cell biology of the reaction. One major hypothesis to be tested is that factors closely related to blood pressure may directly affect the intima - i.e., that blood pressure may correlate with certain intimal ultrastructural alterations independently of the hormonal-biochemical milieu in diverse hypertensive and stressed states. Alternatively, changes in the levels of hormones such as renin and sympatho-adrenal hormones may be determined to act independently or to interact with hypertension in their effects on arterial intima. Aspects of intimal pathology and cell biology to be addressed include the following: endothelial morphology, permeability, cellular injury, and adaptive behavior; accumulation of basement membrane, glycosaminoglycan, and plasma proteins in the subendothelial space; and the roles of smooth muscle cells, blood leukocytes, and possibly platelets in the early intimal reaction. This work is viewed as an initial step toward a long-term objective of elucidating the early intimal reaction in many atherogenic metabolic and hemodynamic states.